The trial aim is to ascertain what, if anything, needs to be combined with a boosted protease inhibitor (bPI) backbone in second-line therapy in order to maximize the chance of a good clinical outcome following WHO-defined failure on a first-line nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI-containing regimen with probable extensive NRTI and NNRTI resistance mutations.

The choice of NRTIs will be at the discretion of the managing clinician and based on the local standard of care and drug availability, taking into account patient's previous drug exposure and side effects on first-line therapy.

Experimental: bPI + raltegravir

Drug: Aluvia + raltegravir

Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily

raltegravir (400mg) twice daily

Experimental: bPI monotherapy

Drug: Aluvia monotherapy

Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily

raltegravir (400mg) twice daily for the first 12 weeks only

Detailed Description:

The standard of care for second-line HIV therapy in patients who have failed a first-line NNRTI-based regimen is to combine a boosted protease inhibitor (bPI) with two (new) NRTIs. However, patients failing first-line therapy in roll-out programmes often have extensive NRTI resistance mutations that may compromise the efficacy of the NRTI drugs used in second-line therapy and it is likely that the virological potency of the second-line regimen is mostly due to the bPI. It is possible that the contribution of the NRTI drugs to efficacy may be outweighed by additional toxicity and cost. It is also possible that replacing the NRTI drugs with a new class of drug (integrase inhibitors) will improve outcome from second-line therapy, although if the boosted protease inhibitor alone is providing close to optimal response, incremental gains from adding a new class may be small.

The principal aims are to determine whether, in patients failing a first-line NRTI and NNRTI-containing regimen:

The use of bPI plus raltegravir (an integrase inhibitor) is superior to standard of care (bPI plus 2 new NRTIs) in achieving good HIV disease control at 96 weeks after randomisation

The use of bPI monotherapy, preceded by a 12-week induction period in combination with raltegravir, is non-inferior to standard of care in achieving good HIV disease control at 96 weeks after randomisation

Requires concomitant medication with known major interactions with study drugs for which drug substitutions or dose alterations are not available or acceptable

Women who are currently pregnant or breastfeeding

Current participation in another clinical trial involving a treatment intervention (may be permitted in some circumstances, but must be discussed with MRC CTU)

Life expectancy of less than one month in the opinion of the treating physician

Contacts and Locations

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For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00988039

Uganda: National Council for Science and TechnologyUganda: National Drug AuthorityZimbabwe: Medicines Control Authority of ZimbabweMalawi: Pharmacy, Medicines and Poisons BoardZambia: Zambia Pharmaceutical Regulatory AuthorityKenya: Pharmacy and Poisons Board